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1. Xenobiotica. 2012 Feb 21. [Epub ahead of print]

Reversal of P-glycoprotein-mediated multidrug resistance in human hepatoma cells
by hedyotiscone A, a compound isolated from Hedyotis corymbosa.

Gar-Lee Yue G, Kin-Ming Lee J, Cheng L, Chung-Lap Chan B, Jiang L, Fung KP, Leung
PC, Bik-San Lau C.

Institute of Chinese Medicine , Shatin, New Territories, Hong Kong , China.

Multidrug resistance is a major problem in hepatocellular carcinoma. Hedyotiscone
A, a compound isolated from Chinese herbal medicine Hedyotis corymbosa (HC,
family Rubiaceae), was used as the chemical marker to distinguish between HC and
an anticancer herb Hedyotis diffusa (HD) in our previous study. The present study
aimed to investigate whether HA exhibited antiproliferative activities in
multidrug-resistant hepatocellular carcinoma cells R-HepG2 and the parental cells
HepG2 using MTT assay and [(3)H]-thymidine incorporation assay. Our results
showed that HA could significantly inhibit cell proliferation in R-HepG2 and
HepG2 (IC(50) = 43.7 and 56.3 µg/mL, respectively), but not in normal human liver
cells WRL-68 (IC(50) > 100 µg/mL) cells, suggesting its selective cytotoxic
effects. Besides, HA induced apoptosis in R-HepG2 cells, as confirmed by
annexin-V & propidium iodide staining, and DNA fragmentation assay. The caspase
cascade was activated as shown by a significant increase of cleaved caspases-3,
-7 and -9 in HA-treated R-HepG2 cells. The activities and protein expression of
P-glycoprotein as well as mRNA expression of MDR1 were also decreased in
HA-treated R-HepG2 cells. Our study demonstrated for the first time the
antiproliferative activities of hedyotiscone A in multidrug-resistant R-HepG2
cells. The findings revealed the potential of this compound in treating
multidrug-resistant tumor.

PMID: 22352391 [PubMed - as supplied by publisher]